This proposal describes a four-year training program for the development of an academic career in Laboratory Medicine. The principal investigator has completed fellowship training in Medical Oncology at Memorial Sloan-Kettering Cancer Center and will now expand upon his scientific skills through a unique integration of interdepartmental resources. Alan Houghton will mentor the principal investigator's scientific development. Dr. Houghton is Chairman of the Immunology Program and Chief of the Clinical Immunology Service at MSKCC, and an authority on tumor immunology. To enhance the training, the program will enlist the expertise of Dr. Eric Pamer, Chief of the Infectious Disease Service at MSKCC, and a recognized expert on the use of mouse models for the study of T cell responses to pathogens. In addition, an advisory committee of highly regarded medical scientists will provide scientific and career advice. [unreadable] [unreadable] Research will focus on the generation of T cell memory responses to melanoma differentiation antigens in a mouse pre-clinical model. The specific aims include: (1) Characterizing the generation of CD8+ T cells against melanoma differentiation antigens by xenogeneic DNA immunization; (2) Investigating mechanisms necessary for the maintenance of CD8+ T cells specific for differentiation antigens, including the role of antigen expression, CD4 help and immune tolerance; and (3) Developing strategies to induce memory T cells against tumor antigens, including the co-delivery of cytokine genes acting as molecular adjuvants, and examining the effects of CTLA-4 blockade and regulatory T cells. These studies are directly relevant to a class of common antigens expressed by many if not most human cancers and hopefully will lead to improved strategies for immunization against these antigens in humans with cancer. [unreadable] [unreadable] The Department of Medicine at Memorial Sloan-Kettering Cancer Center provides an ideal setting for training physician scientists by incorporating expertise from diverse resources into customized programs. This environment maximizes the potential for the principal investigator to establish a successful independent research program. [unreadable] [unreadable]